Download Graded persistent activity in entorhinal cortex neurons

Graded persistent activity in
entorhinal cortex neurons
A.V.Egorov, B.N.Hamam, E.Fransen, M.E. Hsselmo, and A.A.Alonso
발표자: 심리학과 생물심리전공 설선혜
Introduction

Medial-temporal lobe
memory system

Entorhinal cortex (EC) in the
parahippocampal region is
crucially involved in the
acquisition, consolidation
and retrieval of long-term
memory traces for which
working memory operation
are essential.
EC is the crucial component
of the medial temporal-lobe
memory system.

(Kandel et al., Principles of Neural Science 4th ed.)
Introduction

Memory system and Working memory
(http://www.psy.ohio-state.edu/psy312/wrkmem.html)
Introduction

Activity of a cell in the
Inferotemporal cortex of a monkey
in a visual memory task
(Fuster,1997)
Persistent neuronal activity is the
elementary process underlying working
memory

EC neurons also display
persistent activity during the
delay phase of delayed match or
non-match tasks.
Introduction

What is the cellular
basis of the persistent
neuronal activity?
Synaptic reverberations in
recurrent circuits
Vs
Intrinsic neuronal ability
Method

Individual neurons from layer V of
the entorhinal cortex were
recorded.
(Young et al., 1997)
Method

Intracellular recording method in a rat EC
slice preparation
(Hammond, 2001,Cellular and Molecular Neurobiology)
(Klink and Alonso, 1997)
(Henze et al., 2000)
Result: Muscarinic
dependent persistent
activity

Figure 1: Muscarinic dependent
persistent activity
a. CCh or muscarine could give rise to a plateau
potential, which was blocked by atropine or
pirenzepine.
muscarinic-dependent
b, c. increases in the stimulus duration or intensity
led to an increase in the duration of the plateau
potential.
activity dependent and self sustained
d. voltage dependence of persistent firing.
Result:
Muscarinic dependent persistent activity

The muscarinic-dependent plateau potential were not caused by local circuit
reverberation mechanisms.
 Activities were recorded during glutamatergic and GABA-mediated neurotransmission block with
cocktails consisting of a mixture of kynurenic acid and picrotoxin.
Nevertheless, the plateau activity could be induced equally well with synaptic stimulation during
intact neurotransmission.
Intrinsic!
Result

Persistent activity for working memory can directly encode dimensions of
input or output signals if it can maintain stable analogue values of activity.
(Seung et al., 2000)
Result: Graded persistent activity

Figure 2a : Repetitive depolarizing steps
Result: Graded persistent activity

Figure 2c: Repetitive hyperpolarizing steps
Result: Graded persistent activity

Figure 2b: Fourier analysis plots
Depolarizing step(15)
Hyperpolarizing step(51)
Result: Graded persistent activity

Repetitive application of the sustained firing inducing input always led to
well-defined increases of stable discharge rates. (Graded)

Once persistent firing was initiated it could only be turned off by prolonged
membrane hyperpolarizations. (Persistent)

Repetitive application of hyperpolarizing current pulse steps lead to graded
stable decreases in firing rate.

And then,
Could local synaptic activation also lead to a state of persistent firing?
Result:
Synaptic induction of persistent activity

Figure 3a
Result:
Synaptic induction of persistent activity

Figure 3b: stable increase in frequency by synaptic excitation
Result:
Synaptic induction of persistent activity

Figure 3c: synaptic inhibition with 1mM kynurenic acid
Result:
Synaptic induction of persistent activity

Muscarinic modulation of EC layer V neurons implements in these neurons
the internal ability to generate truly persistent activity that can maintain
multiple levels of stable firing rate.

It should be resistant to distracting inputs.
 stable firing frequency were not affected by relatively brief excitatory-inhibitory stimuli.
Result: Ionic mechanism

Ca2+ influx associated with spiking is an important element.

Figure 4a: removal of extracellular Ca2+ completely and reversibly abolished muscarinic induced
plateau potentials

Intracellular injection of the Ca2+ chelator EGTA had the similar effect.
The induction of the plateau potential depends on intracellular Ca2+ rises.
Result: Ionic mechanism

4b: nifedipine partially
blocked the activity.
 L-type channels are related.
4c: flufenamic acid
completely blocked the
persistent activity.
 Ca2+ -activated non-specific
cation current is important.

Spike-induced Ca2+ influx triggering a slow potential mediated by a cationic
current can be a basic mechanism for the generation of persistent activity.
Conclusion

EC layer V neurons lie at the core of the hippocampal neocortical memory
system, which implements the acquisition, storage and retrieval of
memories for facts and events in a temporally organized and graded
manner.

The single-cell mnemonic mechanism

allows cells to ‘hold on’ to information for relatively prolonged periods of time
enables the system to perform associational computations

It might be fundamental for the memory operations in the temporal lobe.
Conclusion

Working Memory

While working memory operations in prefrontal cortex may be important for monitoring familiar
stimuli, the medial temporal lobe may be more important for matching and active maintenance of
mew information during memory delays (Stern et al., 2001).
Perirhinal and entorhinal lesions impaired neuronal responses to visual paired associates in
inferotemporal cortex (Higuchi and Miyashita, 1996).

The intrinsic persistent activity displayed by the EC layer V cells represents
an ideal mechanism for sustaining information about a new stimulus for
memory encoding and/or consolidation purposes.
Conclusion
Synaptic reverberations in recurrent circuits Vs
Intrinsic neuronal ability
Conclusion

EC layer V neurons behave as analogue memory devices.

muliple bits of information in the form of activity along a graded dimension determined by stimulus
input.
※bistable neurons
(Marder et al.,1996)
This intrinsic cellular behavior constitutes an elementary form of
mnemonic process on which associative network mechanisms could build
to hold externally or internally driven sensory representations.
Conclusion


Memory in networks results from an ongoing interplay between changes in
synaptic efficacy and intrinsic membrane properties. (Marder et al., 1996)
Changes in…
synaptic efficacy + intrinsic membrane properties  Memory
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Supplementary Information
Supplementary Information
Appendix